{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T06:25:15Z","timestamp":1787034315697,"version":"build-2736575974"},"reference-count":15,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The Echinoderm microtubule-associated protein-like 4 (EML4) - Anaplastic lymphoma kinase (ALK) gene fusion represents a significant driver mutation in non-small cell lung cancer (NSCLC). Among the over 20 identified EML4-ALK variant subtypes, the V5' variant occurs relatively infrequently, constituting merely 4% of cases. Currently, the clinicopathological features and prognostic implications associated with this particular variant remain poorly characterized in the literature.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case summary<\/jats:title>\n                    <jats:p>We report the case of a 38-year-old man diagnosed with stage IV lung adenocarcinoma carrying the EML4-ALK V5' fusion variant, who received first-line treatment with iruplinalkib at a dose of 180\u00a0mg once daily. After 6.3\u00a0months of therapy, the patient developed a substantial malignant pleural effusion. Consequently, the treatment regimen was switched to lorlatinib 100\u00a0mg once daily combined with intrathoracic infusion chemotherapy. However, no significant improvement in the malignant pleural effusion was observed. We thereafter modified the therapeutic strategy to include lorlatinib-based targeted therapy combined with a dual-agent chemotherapy regimen consisting of cisplatin and pemetrexed, along with bevacizumab for anti-angiogenic therapy. Following this adjustment, the patient\u2019s malignant pleural effusion showed marked remission.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>For patients with NSCLC harboring the EML4-ALK V5' fusion variant who have developed resistance to second-generation tyrosine kinase inhibitors (TKIs), switching to third-generation TKI lorlatinib in combination with chemotherapy and anti-angiogenic treatment may serve as a potential therapeutic option for overcoming acquired resistance and curbing rapid disease progression.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1876652","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:36:56Z","timestamp":1787031416000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Report: Lorlatinib combined with chemotherapy and anti-angiogenic therapy shows promising efficacy in an ALK gene fusion lung adenocarcinoma patient with iruplinalkib resistance"],"prefix":"10.3389","volume":"17","author":[{"given":"Mengqing","family":"Cao","sequence":"first","affiliation":[{"name":"Department of Respiratory Medicine, The Second Affiliated Hospital of Jiaxing University","place":["Jiaxing, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shumin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, The Second Affiliated Hospital of Jiaxing University","place":["Jiaxing, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linfeng","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, The Second Affiliated Hospital of Jiaxing University","place":["Jiaxing, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Tao","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, The Second Affiliated Hospital of Jiaxing University","place":["Jiaxing, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, The Second Affiliated Hospital of Jiaxing University","place":["Jiaxing, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1184","DOI":"10.3390\/cancers14051184","article-title":"Review of therapeutic strategies for anaplastic lymphoma kinase-rearranged non-small cell lung cancer","volume":"14","author":"Fukui","year":"2022","journal-title":"Cancers"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1901","DOI":"10.1016\/j.jtho.2019.08.003","article-title":"Monitoring therapeutic response and resistance: analysis of circulating tumor DNA in patients with ALK+ lung cancer","volume":"14","author":"Horn","year":"2019","journal-title":"J. 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Soc. Med. Oncol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"157","DOI":"10.3390\/medicina60010157","article-title":"Reduced-dose or discontinuation of bevacizumab might be considered after variceal bleeding in patients with hepatocellular carcinoma receiving atezolizumab\/bevacizumab: case reports","volume":"60","author":"Yeom","year":"2024","journal-title":"Med. Kaunas. Lith."},{"key":"B14","doi-asserted-by":"publisher","first-page":"3383","DOI":"10.1200\/JCO.2015.65.8732","article-title":"Differential crizotinib response duration among ALK fusion variants in ALK-positive non-small-cell lung cancer","volume":"34","author":"Yoshida","year":"2016","journal-title":"J. Clinical Oncology Official Journal Am. Soc. Clin. Oncol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1016\/j.lungcan.2021.06.012","article-title":"Going beneath the tip of the iceberg. Identifying and understanding EML4-ALK variants and TP53 mutations to optimize treatment of ALK fusion positive (ALK+) NSCLC","volume":"158","author":"Zhang","year":"2021","journal-title":"Lung Cancer Amsterdam, Neth."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1876652\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:36:59Z","timestamp":1787031419000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1876652\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,18]]},"references-count":15,"alternative-id":["10.3389\/fphar.2026.1876652"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2026.1876652","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,18]]},"article-number":"1876652"}}